담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

제대혈 유래 인간 비만세포에서의 세포증식 및 히스타민 분비에 대한 Interleukin 9의 영향

안강모 ( Kang Mo Ahn ),이광신 ( Kwang Shin Lee ),신미용 ( Mi Yong Shin ),박화영 ( Hwa Young Park ),안연화 ( Yeon Hwa Ahn ),손대열 ( Dae Yeul Son ),이상일 ( Sang Il Lee ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2002 소아알레르기 및 호흡기학회지 Vol.12 No.4

목적: Interleukin 9(IL-9)는 Th2 싸이토카인의 일종으로서 알레르기 염증반응의 병태생리에 관여하는 것으로 알려져 있다. 본 연구에서는 IL-9이 주요 알레르기 염증세포의 하나인 인간 비만세포에 어떠한 영향을 주는지를 알아보기 위하여 시행되었다. 방법:본 연구에서는 인간 제대혈에서 CD34 (+) 세포를 분리한 후 stem cell factor(SCF), IL-3, IL-6를 투여함으로써 비만세포를 선택적으로 배양하였다. 8주간 배양이 끝 Purpose:Interleukin-9(IL-9), one of Th2-type cytokines, might be important in the pathophysiology of allergic diseases. We investigated the effect of IL-9 on human mast cells by assessing cell proliferation and histamine release. Methods: Human umbilical

골수이식 후 사이토카인과 골교체 생화학적표지자의 변화 및 상관관계

민우성,강무일,한제호,강성구,오기원,이원영,김혜수,문성대,손현식,신완식,김춘추,윤건호,차봉연,이광우,손호영 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.1

Background : Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. Methods : This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-? at post-BMT 3 week and bone turnover marker at the same time to assess the relationship beween two parameters. Results : Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-? or peripheral blood cytokines was not found. Conclusion : Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo(J Kor Soc Endocrinol 15:85-96, 2000).

Nicotine Suppresses TNF-${\alpha}$ Expression in Human Fetal Astrocyte through the Modulation of Nuclear Factor-${\kappa}B$ Activation

Son, Il-Hong,Park, Yong-Hoon,Yang, Hyun-Duk,Lee, Sung-Ik,Han, Sun-Jung,Lee, Jai-Kyoo,Ha, Dae-Ho,Kang, Hyung-Won,Park, Joo-Young,Lee, Sung-Soo The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.2

Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

미세 전기기계 시스템용 알루미늄 박막의 탄성계수 및 항복강도 평가

주영창,손동일,관동일 대한금속재료학회(대한금속학회) 2001 대한금속·재료학회지 Vol.39 No.3

Nowadays, the aluminum films have wide application in micromechanical devices such as micro sensors and actuators, so that their mechanical properties come to be very important for reliability evaluation. However, there is no standardized method to evaluate the mechanical properties of material used in MEMS (micraelectromechanical system) device since the measured mechanical properties are influenced by many factors such as surface condition, friction force, etc. Hence, we intended to evaluate the mechanical properties of thin film in our study, which is important in mechanical operation. Because MEMS devices are usually operating in elastic range, the Young's modules and yield strength were evaluated by using microcantilever beam technique. First, Al cantilever beams were fabricated using the silicon bulk micromachining technology to have various film thickness. And then, the load-displacement curve was obtained by nanoindentation method. The linear relation in elastic range was utilized in deriving the Young's modulus of Al film, which gives us reproducible result regardless of film thickness. In high load range, the deviation from the linear relation was detected, so that the yield strength of Al film could be evaluated. It is found that the yield strength increases with decreasing film thickness. By applying the misfit dislocation theory and the Hall-Petch relation, the theoretical estimation could predict well the trend of yield strength.

동종골수이식 후 발생한 비갑상선질환 증후군에서 사이토카인의 혈청 농도의 변화 및 비갑상선질환 증후군이 이식 후 예후에 미치는 영향

안병영,이광우,민우성,손형선,손호영,차봉연,강무일,윤건호,강성구,오기원,이원영,손현식,신완식,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.2

Background : Alteration of thyroid hormone parameters are frequently observed in sick patients and commonly known as nonthyroidal illness syndrome(NTIS) or euthyroid sick syndrome(ESS). NTIS is seen in starvation, surgery, severe illness, and also bone marrow transplantation(BMT). The degree of reduction in thyroid hormone parameters correlated with the severity of NTIS and might predict the prognosis of underlying illness. Recently, particular attention is focused on the role of cytokines in developing the NTIS. This prospective study was designed to assess the relationship of serum thyroid hormone parameters and serum cytokine levels before and in the short-term follow-up after allogeneic BMT in order to predict patients outcome. Methods : Included 80 patients that were mainly leukemia and severe aplastic anemia. Serum thyroid hormone parameters and serum cytokine levels were measured before and 7, 14, 21, 28 days and 3, and 6 months after BMT. Results : Near-all patients experienced significant decrease of thyroid hormone levels and also significant increase of cytokine levels after BMT. After post-BMT 3 weeks, the serum cytokine levels were negatively correlated with the serum T3 and T4 levels, but not with the serum TSH levels. The patients treated with high-dose steroid or total-body irradiation tended to show lower levels of TSH and more delayed recovery compared to non-treated patients. The patients died after BMT represented generally lower levels of all thyroid hormone parameters than survival patients during entire follow-up period. Conclusion : Development of NTIS is associated with higher probability of fatal outcome after BMT and has prognostic relationship in this group of patients. Increased levels of cytokines, especially IL-6 and TNF-?, are often found in post-BMT NTIS patients and correlated with the changes in the levels of thyroid hormone parameters(J Kor Soc Endocrinol 15:214-225, 2000).

참돔(Pagrus major) Interleunkin 7 receptor alpha chain (IL-7Rα) 유전자의 분자유전학적 특성 및 발현분석

손민영(Min-Young SON),최광민(Kwang-Min CHOI),주민수(Min-Soo JOO),박찬일(Chan-Il PARK) 한국수산해양교육학회 2020 水産海洋敎育硏究 Vol.32 No.2

노화가 인체 중간엽 줄기세포로부터 조골세포로의 증식 및 분화에 미치는 영향

백기현,태현정,오기원,이원영,조정기,권순용,강무일,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.3

연구배경: 일반적으로 골다공증과 연관된 위험인자로는 연령, 폐경, 약물, 불충분한 칼슘섭취, 만성질환 및 운동부족 등이 있는데, 특히 노화가 진행할수록 골밀도가 감소하는 것은 잘 알려져 있다. 노화와 관련하여 진행되는 골소실은 조골세포 및 전구조골세포의 기능적 결핍에 의한 골형성의 감소가 주요한 요인으로 여겨지고 있다. 그 동안 연령이 조골모 세포의 양과 조골모 세포로부터 성숙조골세포로의 분화 및 증식에 미치는 영향에 대한 일부 보고들이 있었으나 아직 일치된 견해는 없는 형편이다. 방법: 다양한 연령의 사람으로부터 골수를 채취, 중간엽 줄기세포가 포함된 단핵세포를 분리한 후 조골세포로 분화하기 좋은 조건하에서 배양하였다. 대상군은다시 젊은군과 노령군으로 구분하여 다양한 변수를 비교 분석하였다. 일차배양에서는 CFU-F를 계수하여 골수내 중간엽 줄기세포의 수를 추산하였고, 칼슘측정을 통하여 기질의 무기화 정도를 비교하였다. 계대배양후 이차배양에서는 시기별로 알카리성 포스파타제 활성도를 측정하고 오스테오칼신 mRNA의 발현을 관찰하여 젊은군과 노령군 사이의 증식능 차이를 비교하였다. 또한 이차배양 시기별로 MTT 측정을 하여 양군간에 증식능 차이가 있는지 알아보았다. 결과: 1. 일차배양 15일째에 평균 CFU-F의 수는 젊은군에서 유의하게 많았다(젊은군 148.3±28.9, 노령군 54.3±9.1, p=0.02). CFU-F의 평균면적은 젊은군에서 넓은 경향을 보였으나 통계적으로 유의하지는 않았다. 2. 일차배양 17일 경과 후 양군간에 기질 칼슘 침착정도는 유의한 차이를 보이지 않았다(젊은군 103.6±50.6, 노령군: 114.0±56.5, p=NS). 3. 이차배양 10일째에 젊은군에서 알카리성 포스파타제 활성도가 고령군에 비해 유의하게 높았다(젊은군: 935.5±115.0 U/mg, 노령군: 578.4±115.7U/mg,p.0.05). 고령군에서는 시간 경과에 따른 변화가 미약했으며 전반적으로 알카리성 포스파타제의 활성도가 젊은군에 비해 낮았다. 4. 이차배양도중 오스테오칼신 mRNA의 발현은 배양시기별로 젊은군에 비해 고령군에서 더 낮은 경향을 관찰할 수 있었다. 5. 이차배양 10일과 15일에 젊은군에서 노령군보다세포증식이 유의하게 증가된 양상을 보였다(10앓 젊은군 0.73±0.05, 노령군 0.58±0.04, p=0.05, 15일; 젊은군 0.80±0.05, 노령군 0.70±0.03, p=0.05).결론: 이상의 연구에서 저자들은 노령군에서 젊은군보다 골수 내 중간엽줄기세포의 수가 적고, 노령군에서 유래한 전구조골세포의 성숙조골세포로의 증식 및 분화가 젊은군 보다 감소해 있는 것을 관찰할 수 있었다. Background: Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFL-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. Methods: Bone marrow was obtained from the iliac crest of young (n=6, 27.2±8.6 years old) and old (n= 10, 57.4k6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcin expression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. Results: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3±28.9, old: 54.3±9.1, p=0.02) and the mean size of CFL-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6±50.6, old: 114.0±56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5±115.OU/mg, old: 578.4±115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. Conclusion: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging (J Kor SOC Endocrinol 18:296-305, 2003).

탈미네랄화 골분(DBP)이 PLGA 지지체의 염증반응을 완화시킨다

최방실 ( Bang Sil Choi ),김순희 ( Soon Hee Kim ),윤선중 ( Sun Jung Yun ),하현정 ( Hyun Jung Ha ),김문석 ( Moon Suk Kim ),양영일 ( Young Il Yang ),손영숙 ( Young Sook Son ),강길선 ( Gil Son Khang ),이종문 ( John M. Rhee ),이해방 ( 한국조직공학과 재생의학회 2006 조직공학과 재생의학 Vol.3 No.3

We developed the demineralized bone particle(DBP) impregnated poly(lactide-co-glycolide)(PLGA) scaffolds(PLGA/DBP) to investigate the effect of adhesion, growth, viability and inflammatory reaction of the cells. PLGA/DBP scaffolds were prepared by solvent casting/salt leaching method and were characterized by porosimeter, and scanning electron microscopy. NIH/3T3 fibroblast cells were cultured in the PLGA/DBP scaffolds as well as film and MTT assay was used to assess the viability of cells. Also, human promyelocytic leukemia cells(HL-60) were cultured in the PLGA/DBP scaffolds. We observed IL-1ß? and TNF-α expression of HL-60 cells seeded in PLGA/DBP scaffold by RT-PCR. NIH/3T3 fibroblast cell seeded on PLGA/DBP film were more adhere and spread with increasing DBP content due to increasing hydrophilicity and bioactivity. The fluorescence intensity of the band of TNF-α and IL-1ß? gene was decreased with increasing the concentration of DBP. It seems that the DBP affected on the improvement of physicochemical properties of PLGA such as biocompatibility, wettability and inflammatory response.

하악 제3대구치 발거 시기가 Ⅲ급 부정교합의 치료에 미치는 영향 : Effect of the lower third molar on the treatment of Class Ⅲ malocclusion

손명호,장영일 대한치과교정학회 2004 대한치과교정학회지 Vol.34 No.5

본 연구의 목적은 Ⅲ급 부정교합의 치료 시에 하악 제3대구치의 존재가 하악 치열의 원심 치군 이동(distal en masse movement) 및 치료 기간에 미치는 영향을 평가하기 위한 것이다. 서울대학교병원 교정과에 내원하여 Ⅲ급 부정교합으로 진단을 받고, 이에 대한 교정 치료를 받은 36명(남자 9명, 여자 27명)을 선택하였다. 모든 환자는 제3대구치 이외의 다른 치아는 발거하지 않았다. 이를 하악 제 3대구치의 발거 시기에 따라 세 군으로 분류하였는데, 제1군은 하악 제 3대구치를 발거하지 않고 MEAW를 사용하여 치료를 종료한 12명이며, 제 2군은 MEAW 적용 후에 하악 제 3대구치를 발거한 8명, 제 3군은 MEAW를 적용하기 전에 하악 제3대구치를 발거한 16명이다. 각 환자들에 대하여. 전체 치료 기간 및 MEAW 적용 기간을 구하였으며, 치료 전 후의 측모 두부 계측 방사선 사진을 분석하였다. 각 군에 대한 치료 기간 및 치료 전 후의 변화를 ANOVA를 이용하여 통계 처리 하였으며. 다음과 같은 결론을 얻었다. 전체 치료 기간은 각 군 사에 유의성 있는 차이가 없었으나, MEAW를 적용한 기간은 제 2군(MEAW 적용 후에 하악 제3대구치를 발거한 군)에서 가장 길었다. 제3군(MEAW를 적용하기 전에 하악 제3대구치를 발거한 군)에서, 치료 후에 형성된 overjet이 가장 컸다. 제3군(MEAW를 적용하기 전에 하악 제3대구치를 발거한 군)의 경우 치료 후에 IMPA가 감소화였으나, 제1군(하악 제3대구치를 발거하지 않고 치료를 종료한 군)과 제 2군(MEAW 적용 후에 하악 제3대구치를 발거한 군)에서는 IMPA가 증가하였다. 제2대구치의 원심 치체 이동량은 세 군 사이에 유의성 있는 차이가 없었으나, 원심 경사 이동량은 세 군 사이에 통계적으로 유의한 차이가 있었으며, 제 2군, 제 3군, 제 1군의 순이었다. 따라서, MEAW를 적용하기 이전에 하악 제3대구치를 발거하는 것이 Ⅲ급 부정교합의 교정적 치료에 더 좋을 것으로 판단된다. 제 2군의 경우 하악골의 전방 회전 결과, 하악 평면각의 감소가 있었으며. 이러한 골격 변화가 치료 기간의 연장에 영향을 주었다고 판단된다. The purpose of this study was to evaluate the effect of the lower third molar on treatment time and distal en masse movement of the lower dentition in Class Ⅲmalocclusions. Thirty subjects (9 males and 27 females) were selected, all of whom were diagnosed as Class Ⅲ malocclusion and treated by fixed appliances without premolar and/or molar extraction. They were divided into three groups. Group 1 consisted of 12 subjects, whose lower third molars were not extracted during the whole orthodontic treatment. Group 2 consisted of 8 subjects, whose lower third molars were extracted after MEAW application and before removal of the orthodontic appliances. Group 3 consisted of 16 subjects, whose lower third molars were extracted before MEAW application. For each subject, overall treatment time and duration of MEAW application were determined. In addition, pre-treatment and post- treatment lateral cephalometric radiographs were analyzed. All data were processed statistically with ANOVA, and the conclusions were as follows: There was no significant difference among the groups in overall treatment time. However, duration of MEAW application was longer in Group 2 than in Group 1 or Group 3. The overjet that was established after orthodontic treatment was largest in Group 3, in which the lower third molars were extracted before MEAW application. After orthodontic treatment, IMPA decreased in Group 3, but increased in Group 1 and Group 2. There was no significant difference among the three groups in the translation of lower second molars. However, the tipping movement of lower second molars was significantly different, highest In Group 2 and lowest in Group 1. Therefore, it is thought to be better for the orthodontic treatment of Class Ⅲ malocclusions to extract the lower third molars before MEAW application. In Group 2, the mandibular plane angle was decreased as a result of forward rotation of the mandible. This skeletal change was thought to bring about the difficulty of treatment.